Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Chemoradiation for the Treatment of Oral Cancers

NCT ID: NCT03515538

Last Updated: 2024-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-12
• Study Completion Date: 2020-10-08

Brief Summary

The purpose of this study is to determine if RRx-001, which is added on to the cisplatin and radiation treatment, reduces the duration or length of severe oral mucositis in patients with head and neck cancers. All patients in this study will receive 7 weeks of standard of care radiation therapy given with the chemotherapy agent, cisplatin. Patients in arms 1, 2 and 3 will also receive RRx-001 on different schedules.

Detailed Description

The standard treatment for head and neck cancer currently includes a chemotherapy drug called cisplatin that is given by intravenous (IV) infusion and radiation, which is delivered from a machine that precisely targets the tumor. One common and unfortunate side effect of treatment with cisplatin and radiation is oral mucositis, which refers to irritation of the lining of the mouth. Oral mucositis is a serious problem 1) because the open mouth sores from oral mucositis may lead to severe pain, nutritional problems and dehydration from an inability to eat and drink, an increased risk of infection from bacteria and fungus and delay or discontinuation of treatment and 2) because there is only one approved therapy to treat or prevent it.

Conditions

Oral Mucositis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

RRx-001 Pre-Treatment plus SOC

Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC (four doses total). No additional RRx-001 will be given during the course of RT/cisplatin

Group Type: EXPERIMENTAL

RRx-001

Intervention Type: DRUG

RRx-001 for injection

Cisplatin for injection

Intervention Type: DRUG

Patients will receive 3 doses of cisplatin at 100 mg/m2 in accordance with applicable guidelines such as NCCN; however, these guidelines are not intended to supersede or replace institutional guidelines with respect to appropriate and necessary care for individual patients

Radiation Therapy

Intervention Type: RADIATION

Intensity Modulated Radiation Therapy (IMRT) in accordance with the American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) Practice Guideline for IMRT) is mandatory for this study

RRx-001 Pre-Treatment, 2 Concurrent Doses plus SOC

Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC. In addition, one dose of RRx-001 will be given on the last radiation day in each of weeks 2 and 5 during RT/cisplatin administration

Group Type: EXPERIMENTAL

RRx-001

Intervention Type: DRUG

RRx-001 for injection

Cisplatin for injection

Intervention Type: DRUG

Patients will receive 3 doses of cisplatin at 100 mg/m2 in accordance with applicable guidelines such as NCCN; however, these guidelines are not intended to supersede or replace institutional guidelines with respect to appropriate and necessary care for individual patients

Radiation Therapy

Intervention Type: RADIATION

Intensity Modulated Radiation Therapy (IMRT) in accordance with the American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) Practice Guideline for IMRT) is mandatory for this study

RRx-001 Pre-Treatment, 6 Concurrent Doses plus SOC

Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC. In addition, one dose of RRx-001 will be given on the last radiation day of each of the first 6 weeks during RT/cisplatin administration

Group Type: EXPERIMENTAL

RRx-001

Intervention Type: DRUG

RRx-001 for injection

Cisplatin for injection

Intervention Type: DRUG

Patients will receive 3 doses of cisplatin at 100 mg/m2 in accordance with applicable guidelines such as NCCN; however, these guidelines are not intended to supersede or replace institutional guidelines with respect to appropriate and necessary care for individual patients

Radiation Therapy

Intervention Type: RADIATION

Intensity Modulated Radiation Therapy (IMRT) in accordance with the American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) Practice Guideline for IMRT) is mandatory for this study

Standard of Care

No doses of RRx-001 will be administered. Patients assigned to this arm will receive only standard of care in the form of a 7-week course of fractionated radiation therapy concurrent with a high-dose cisplatin regimen (100 mg/m2 dose in each of RT weeks 1, 4, and 7).

Group Type: ACTIVE_COMPARATOR

Cisplatin for injection

Intervention Type: DRUG

Patients will receive 3 doses of cisplatin at 100 mg/m2 in accordance with applicable guidelines such as NCCN; however, these guidelines are not intended to supersede or replace institutional guidelines with respect to appropriate and necessary care for individual patients

Radiation Therapy

Intervention Type: RADIATION

Intensity Modulated Radiation Therapy (IMRT) in accordance with the American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) Practice Guideline for IMRT) is mandatory for this study

Interventions

RRx-001

RRx-001 for injection

Intervention Type: DRUG

Cisplatin for injection

Patients will receive 3 doses of cisplatin at 100 mg/m2 in accordance with applicable guidelines such as NCCN; however, these guidelines are not intended to supersede or replace institutional guidelines with respect to appropriate and necessary care for individual patients

Intervention Type: DRUG

Radiation Therapy

Intensity Modulated Radiation Therapy (IMRT) in accordance with the American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) Practice Guideline for IMRT) is mandatory for this study

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. Pathologically confirmed diagnosis of squamous cell carcinoma (SCC) of the oral cavity and oropharynx Note: Patients with unknown primary tumors whose treatment plan matches the requirements specified in Inclusion Criterion #3 below are eligible for the trial

2. Treatment planned to include standard cisplatin monotherapy administered either every three weeks (100 mg/m2 for 3 doses) with concomitant radiation delivered as a continuous course of IMRT with single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose between 60 Gy and 72 Gy. Planned radiation treatment fields must include at least two oral sites (buccal mucosa, floor of mouth, tongue, soft palate) that are each planned to receive a total of > 55 Gy. Patients who have had prior surgery are eligible, provided they have fully recovered from surgery, and patients who may have surgery in the future are eligible.

3. ECOG performance status ≤ 2.

4. Participants must have adequate organ and marrow function as defined below:

A. Absolute neutrophil count (ANC) >1,500 / mm3 B. Platelets > 100,000 / mm3 C. Hemoglobin ≥ 9.0 g/dL

5. Adequate renal and liver function as indicated by:

A. Serum creatinine acceptable for treatment with cisplatin per institutional guidelines) B. Total bilirubin ≤ 1.5 x upper-normal limit (ULN) C. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN D. Alkaline phosphatase ≤ 2.5 x ULN

6. Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test for patients with cancers of the oropharynx, base of tongue, or unknown primary.

7. Age 18 years or older

8. Patient must consent to the access, review and analysis of previous medical and cancer history, including imaging data by the sponsor or a third party nominated by the sponsor.

9. Ability to understand and sign a written informed consent document.

10. Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.

Note: A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been postmenopausal for at least 12 consecutive months

11. Adequate visual access to permit examination of the following oral cavity sites: lips, buccal mucosa, floor of mouth, ventral and lateral tongue and soft palate.

Exclusion Criteria

1. Prior radiation to the head and neck

2. Tumor of the lips, nasopharynx, hypopharynx, larynx, or salivary glands

3. Patients with simultaneous primaries or bilateral tumors

4. Metastatic disease (M1) Stage IV

5. Malignant tumors other than HNC within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator

6. Presence of oral mucositis (WHO Score ≥ Grade 1) or other oral mucosal ulceration at study entry

7. Grade 3 or 4 dysphagia or odynophagia (National Cancer Institute Common Toxicity Criteria, version 5.0) or inability to eat a normal diet

8. Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition for any reason

9. Known history of HIV or active hepatitis B/C (patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible)

10. Any significant medical diseases or conditions, as assessed by the investigators and sponsor that would substantially increase the medical risks of participating in this study (i.e., uncontrolled diabetes, NYHA II-IV congestive heart failure, myocardial infarction within 6 months of study, severe chronic pulmonary disease or active uncontrolled infection, uncontrolled or clinically relevant pulmonary edema).

11. Pregnant or nursing

12. Untreated active oral or dental infection, including severe tooth decay (caries)

13. Known allergies or intolerance to cisplatin and similar platinum-containing compounds

14. Evidence of immediate life-threatening disease or a life expectancy of less than 3 months

15. Receipt of unapproved or off-label medication within 30 days prior to start of study treatment

16. Sjogren syndrome

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Prothex, Inc.

INDUSTRY

Sponsor Role: collaborator

EpicentRx, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bryan Oronsky, MD, PhD

Role: STUDY_DIRECTOR

EpicentRx, Inc.

Locations

John Wayne Cancer Institute @ Providence St. John's Health Center

Santa Monica, California, United States

Centura Health Research Center

Denver, Colorado, United States

George Washington University

Washington D.C., District of Columbia, United States

Florida Hospital

Orlando, Florida, United States

Montefiore Medical Center

The Bronx, New York, United States

East Carolina University

Greenville, North Carolina, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Ballad Health

Johnson City, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

UT Southwestern

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

PR-001

Identifier Type: -

Identifier Source: org_study_id